반응 #74594

반응 방정식

ammonium chloride

Lithium bis(trimethylsilyl)amide

N-(2,4-Dimethoxybenzyl)-1,3,4-thiadiazol-2-amine

5-chloro-2,4-difluorobenzenesulfonyl chloride

→

title compound

수율 58.5%

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

수율 58.5%

용매

water

2-methyltetrahydrofuran

2-methyltetrahydrofuran

반응 조건

후처리

1. 1
   온도the yellow suspension was cooled to −38° C. to −45° C
2. 2
   기타the temperature between −38° C. and −45° C.
3. 3
   기타to give an orange suspension
4. 4
   기타the temperature between −38° C. and −45° C.
5. 5
   기타to give an orange suspension
6. 6
   workup.STIRRINGThe mixture was stirred whist
7. 7
   기타The reaction was quenched
8. 8
   workup.STIRRINGstirred vigorously for 5 minutes
9. 9
   기타to separate
10. 10
    기타The lower layer was removed
11. 11
    세척the organic layer was washed with water (813.6 mL)
12. 12
    농축The organic layer was concentrated in vacuo
13. 13
    기타to give an orange solid which
14. 14
    기타was triturated with isopropyl acetate (1.22 L)

실험 절차

N-(2,4-Dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 248, 203.4 g, 0.809 moles) was dissolved in 2-methyltetrahydrofuran (1.63 L) and the yellow suspension was cooled to −38° C. to −45° C. Lithium bis(trimethylsilyl)amide (890 mL of 1 molar solution in tetrahydrofuran, 0.890 moles) was added slowly over 15 minutes keeping the temperature between −38° C. and −45° C. to give an orange suspension. This orange suspension was stirred at −38° C. to −45° C. for 45 minutes and then a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride, (200 g, 0.809 moles) in 2-methyltetrahydrofuran (407 mL) was added slowly over 20 minutes keeping the temperature between −38° C. and −45° C. to give an orange suspension. The mixture was stirred whist warming to 15° C. over 1 hour. The reaction was quenched by adding a solution of ammonium chloride (203.4 g, 3.80 moles) in water (1.02 L) and stirred vigorously for 5 minutes. The stirring was stopped and the phases allowed to separate. The lower layer was removed and the organic layer was washed with water (813.6 mL). The organic layer was concentrated in vacuo to give an orange solid which was triturated with isopropyl acetate (1.22 L) to give the title compound as a yellow-orange solid (218.6 g).

출처